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Contributors: A Bansal (U of Pennsylvania) | P Dedhia (U of Cincinnati) | A Elebiary (Lahey Clinic) | X Vela (U of El Salvador) | D Thomson (ECU) | P Jawa (ECU) | S Sridharan (Lister Hospital, UK) | F Iannuzsella (IRCCS, Italy) | D Mitema (Johns Hopkins U) | Malvinder Parmar (Northern Ontario, Canada) | Wisit Cheungpasitporn (Mayo)

#KidneyKONNECTION

THE TRAGIC CASE OF "CREATININA"

Issue 3 Volume 2 Year 2015

URL http://goo.gl/QDSB5B

Editor: Tejas Desai | Chief: Cynthia Christiano | Free subscription by emailing myFellowship@ecu.edu

WHERE EARNING A LIVING COULD EARN YOU AN EARLY DEATH

The prevalence of CKD in developing countries is known to be increasing in part due to the burden of emerging non-communicable diseases such as diabetes mellitus, hypertension, and obesity. These CKD risk factors are often associated with adoption of a more sedentary lifestyle. In Central America, however, CKD is currently manifest in epidemic proportions and is being observed in a rather peculiar geo-demographic population in the absence of diabetes and/or hypertension. This CKD of unknown origin is currently termed ?Meso-American Nephropathy?, and it has been gaining some well-deserved attention recently (CNN, NPR, and NBC have carried out features recently), given the concern that it has probably contributed to the premature death of more than 20,000 young men in the affected regions.

Let?s attempt to break down

Mesoamerican Nephropathy. First, ?Meso-America? for the purposes of the this discussion encompasses the geographic regions of Southeastern Mexico, Guatemala, Belize, El Salvador, Honduras, Nicaragua, Costa Rica, and Panama. (Figure 1, source: Wikipedia). From a geodemographic standpoint, the

observed nephropathy shows preponderance for young men (male to female ratio is 3-4:1) typically age 30-50 years, exposed to working under hot conditions in predominantly agricultural communities in the low lying coastal areas. In the lowlands of the Nicaraguan pacific coast, the condition is colloquially referred to as ?creatinina?, and it is the leading cause of death in young men working in sugar cane plantation. In Chichigalpa, Nicaragua, the significantly high

mortality amongst men has led to a nickname for the community of survivors: ?La Isla de Viudas,? or ?The Island of Widows.?

How do these patients present to clinicians? For starters, the disease is quite asymptomatic until late, as is the case with many causes of CKD. Patients typically present with impairment in their glomerular filtration rate (in the absence of diabetes and hypertension per case definition), with additional studies showing rather bland urinary sediment and non-nephrotic range proteinuria typically <1g/24hrs. There is progressive decline in eGFR and many patients progress to ESRD, though the precise natural history of the disease is yet to be defined. There are limited studies looking at the histopathology of the disease, though the predominant finding seems to be tubulo-interstitial scarring, with some case series also demonstrating glomerular

by D. Mitema (@mitemadog)

ischemia and glomerulosclerosis.

The specific cause for MeN remains elusive, though it is speculated to be multifactorial. The Report from the First International Research Workshop on MeN? (available at http://goo.gl/o6A66Y) has proposed the following framework for development of MeN:

("Creatinina" continued)

Currently, one theory that seems to be gaining some traction is that volume depletion (some workers in Nicaragua lose up to 2.6kg per day after working in the hot sun!) coupled with dehydration and hyperosmolarity trigger chronic activation of vasopressin and the aldose reductase pathway. The end result of the chronic activation of these pathways has recently been shown to contribute to renal injury.   To date, no specific nephrotoxin (heavy metals, pesticides etc) has been demonstrated to be the causative agent. Much work still needs to be done to identify the cause of this epidemic of CKD in Central America.

Treatment strategies in the resource limited setting are mainly conservative. Many patients cannot afford renal replacement therapies, and as a result main focus at this time is on prevention. There are now measures in place to provide sugar-cane workers with hydration, rest, and shade in addition to screening them intermittently for kidney disease while additional studies are undertaken to establish the causative agent/mechanism for this disease. For those students/residents/fellows interested in additional resources on this topic, please visit the following links:

- regionalnephropathy.org

- storify.com/nephondemand/meso-american-nephropathy HO

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